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Identification of a Five-Gene Prognostic Model and Its Potential Drug Repurposing in Colorectal Cancer Based on TCGA, GTEx and GEO Databases
Frontiers in Genetics ( IF 3.7 ) Pub Date : 2020-12-18 , DOI: 10.3389/fgene.2020.622659
Feng Yang , Shaoyi Cai , Li Ling , Haiji Zhang , Liang Tao , Qin Wang

Colorectal cancer (CRC) is a major cause of cancer deaths worldwide. Unfortunately, many CRC patients are still being diagnosed at an advanced stage of the cancer, and the 5-year survival rate is only ~30%. Effective prognostic markers of CRC are therefore urgently needed. To address this issue, we performed a detailed bioinformatics analysis based on the Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx), and Gene Expression Omnibus (GEO) databases to identify prognostic biomarkers for CRC, which in turn help in exploring potential drug-repurposing. We identified five hub genes (PGM2, PODXL, RHNO1, SCD, and SEPHS1), which had good performance in survival prediction and might be involved in CRC through three key pathways (“Cell cycle,” “Purine metabolism,” and “Spliceosome” KEGG pathways) identified by a KEGG pathway enrichment analysis. What is more, we performed a co-expression analysis between five hub genes and transcription factors to explore the upstream regulatory region. Furthermore, we screened the potential drug-repurposing for the five hub genes in CRC according to the Binding DB and ZINC15 databases. Taking together, we constructed a five-gene signature to predict overall survival of CRC and found the potential drug-repurposing, which may improve the outcome of CRC in the future.



中文翻译:

基于TCGA,GTEx和GEO数据库的大肠癌五基因预后模型的确定及其潜在的药物用途

大肠癌(CRC)是全世界癌症死亡的主要原因。不幸的是,仍在癌症晚期诊断出许多CRC患者,其5年生存率仅为〜30%。因此,迫切需要有效的CRC预后指标。为了解决这个问题,我们基于癌症基因组图谱(TCGA),基因型组织表达(GTEx)和基因表达综合(GEO)数据库进行了详细的生物信息学分析,以鉴定CRC的预后生物标志物,进而帮助探索CRC。潜在的药物利用。我们鉴定了五个集线器基因(PGM2,PODXL,RHNO1,SCD和SEPHS1),它们在生存预测中表现良好,并可能通过三个关键途径(“细胞周期”,“嘌呤代谢”和“剪接体”)参与CRC。 KEGG途径)通过KEGG途径富集分析确定。此外,我们在五个中枢基因和转录因子之间进行了共表达分析,以探索上游调节区域。此外,我们根据Binding DB和ZINC15数据库筛选了CRC中五个中枢基因的潜在药物替代用途。综上所述,我们构建了一个五基因签名来预测CRC的总体存活率,并发现了潜在的药物替代用途,这可能会在将来改善CRC的疗效。

更新日期:2021-01-18
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